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Abstract

Introduction: Iron status and iron-regulatory hormone hepcidin have found to be associated with cardiovascular disease and established heart failure (HF). However, their role in the development of new onset HF in currently unknown. This study sought to investigate the association of iron status and hepcidin levels with new onset HF in the community.

Methods: In 6471 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND), a prospective, community-based, cohort study, we analyzed the association between serum hepcidin, parameters of iron status (ferritin, transferrin saturation) and the risk for new onset HF.

Results: Mean age was 53±12 years and 49.3% were male. Median hepcidin concentration was 3.06 (1.67-4.97) nM, median ferritin level was 97 (48-172) ug/L and mean transferrin saturation was 24.8±9.4% (all lower in women; all P<0.001). During a median follow-up of 8.3 years [IQR 7.8-8.9], 203 subjects (3.1%) were newly diagnosed with HF. Per increasing hepcidin or ferritin quintile, a higher annual HF incidence was observed in women (P<0.001), but not in men (Figure 1). Additionally, sex-stratified analyses revealed levels of serum hepcidin as well as ferritin to be associated with new onset HF in women (both P<0.001), whereas this association was not found in men (interaction P=0.014 and P=0.029, respectively). These relationships remained significant in a multivariable model (P=0.039 and P=0.040, respectively) adjusted for established HF risk factors.

Conclusions: In conclusion, both serum hepcidin and ferritin concentration appear to increase the risk for new onset HF in women, but not in men.